Eggan Laboratory

Our research is focused on understanding the contribution of environmental and genetic factors in the development of disease. The relative impact of these factors to pathogenesis is not well understood for many disorders. Complex interactions between genes and the environment have made it particularly difficult to develop accurate models for the sporadic and so called multifactorial forms of human disease.



To further complicate studies, biopsied tissue containing the affected cell type is often extremely limited. Moreover, the developmental or pathological events leading to the disease have usually occurred long before diagnosis. While animal models exist for several diseases, they usually represent a rare, ‘single-hit’, genetic form of a disease that may not completely or accurately reflect the human disorder nor recapitulate the influence of environmental factors in the development of the pathological state.

As a result, it has been extremely difficult to discern the contribution of either genetic or environmental factors in the development of the more common complex diseases, such as type-1 diabetes, Parkinsons and cardiovascular disease. To help overcome these technical difficulties and expand our understanding of these and other complex diseases we are building in vitro models using human embryonic stem cells, in which genetic and developmental aspects of the disease can be controlled.

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 A fundamental understanding of how a cell's identity is determined during differentiation and how it can in turn be manipulated experimentally is a central goal of developmental biology, one with substantial ramifications for biomedicine. We study both the differentiation of embryonic stem cells into the neural lineage and the reprogramming of commonly available differentiated cell types, such as fibroblasts, into either pluripotent stem cells or cells of therapeutic interest, such as spinal motor neuronsTo study differentiation and dedifferentiation, we employ a variety of approaches, including stem cell differentiation, nuclear transfer, and defined reprogramming strategies using known transcriptional regulators and novel small-molecule compounds. 

A number of devastating diseases, including amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), specifically affect the neuromuscular system. Little is known concerning the molecular pathology underlying these conditions, partly because it has been impossible to access significant quantities of the disease-affected cell, the spinal motor neuron. With recent advances in stem cell and reprogramming biology, we can now produce billions of spinal motor neurons with control and diseased genotypes. We use this new resource to design in vitro disease models for both mechanistic studies and for the discovery of novel small-molecule therapeutics.



Human Developmental and Regenerative Biology

Fundamental concepts in developmental biology will be presented within the framework of the developing and regenerating mammal. Where possible, lectures will focus on humans.
Note: This course, when taken for a letter grade, meets the General Education requirement for Science of Living Systems or the Core area requirement for Science B.
Prerequisite: Concurrent enrollment in Life and Physical Sciences A or Life Sciences 1a.

SCRB 302

Mechanisms of Epigenetic Reprogramming